An increase in metabolic demand stimulates an increase in blood flow to active tissue. Within the tissue, arterioles dilate to distribute blood flow to active parenchymal cells they supply. Feed arteries lie external to the tissue and control the magnitude of blood flow entering arteriotar networks 01 the heart, brain, and skeletal muscle. As physical constraints limit direct studies of blood flow regulation by feed arteries in the brain as well as the heart, skeletal muscle can be utilized as a model system to study mechanisms of blood flow regulation through feed arteries in response to metabolic and neural activity. Our laboratory has developed the hamster retractor muscle for this purpose. During skeletal muscle contraction, the increased metabolic demand triggers a dilation that originates in arterioles and "ascends" into their feed arteries via cell-to-cell conduction along endothelial cells and smooth muscle cells that comprise the resistance vascular network. Release of the neurotransmitter, acetyicholine, can elicit a similar response through initiating the conduction of hyperpolarization. Perivascular sympathetic nerves are activated centrally through the neural regulation of blood pressure and peripherally through changes in skeletal muscle length. The central aim of this proposal is to investigate the interaction between sympathetic vasoconstriction and conducted vasodilation in feed arteries using the hamster retractor muscle as a model system. Specifically, in vivo experiments will examine the effect of sympathetic nerve activity on conducted vasodilation triggered by acetylcholine and the effect of sympathetic vasoconstriction on ascending vasodilation in response to muscle fiber recruitment (Aim 1). In vitro studies using isolated, pressurized feed arteries will use electrophysiological measurements to investigate the cellular mechanism by which perivascular nerve activity attenuates conducted hyperpolarization (Aim 2). The long-term goal of the project is to understand how the sympathetic nervous system influences the conduction pathway in feed arteries that control tissue perfusion. Understanding of the sympathetic vasomotor system will add new insight to blood flow regulation and aid in treating stroke, heart attack, and peripheral vascular disease.